1-cyclopropyl-naphthalene derivatives are important intermediates for organic synthesis. For example 1-cyclopropyl naphthalene is used in the manufacture of fungicides, and of pharmaceutically active compounds to treat for example disorders of uric acid metabolism (see e.g. WO 2010/028189) or HIV infections (see e.g. WO 2006/026356). Specific examples of such pharmaceutically active compounds could be 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate or any metabolite, pharmaceutically acceptable salt, solvate, ester, tautomer or prodrug thereof as disclosed in e.g. WO 2009/070740 A2, WO 2011/126852 A2 and WO 2011/159732 A1.
Known synthetic methods for the preparation of cyclopropyl-naphthalene are performed by a palladium-catalyzed Suzuki reaction of an aryl halide with cyclopropyl boronic acid as is disclosed by Lemhadri et. al. in Synthetic Communications (2006) 36(1) 121-128, CN 102391059, and by Zhang et. al. in Tetrahedron (2012), 68(3), 900-905, Suzuki reactions of a heteroaryl mesylate with cyclopropyl trifluoroborate are further disclosed by Molander et. al. in J. Org. Chem. 2011, 76, 8126-8130. A disadvantage of such Suzuki reactions is, the use of expensive starting materials and catalysts which makes such reactions less attractive from a commercial point of view.
Alternatively, reactions of gem-dihalo alkanes with alkenes in the presence of lanthanum metal catalysts are disclosed by Nishiyama et. al. in Tetrahedron Letters (2007), 48(36), 6405-6407. The applied rare earth metal lanthanum is very expensive and is therefore not suitable for use in industrial production.
Processes using Grignard reagents are also known. CN 103664471, discloses reactions of 1-vinylnapthalene with gem-dihalo alkanes with alkyl-MgCl. Kumada coupling reactions of 1-bromonaphthalene with suitable Grignard reagents are disclosed in WO 2014/008295, WO 2012/092395, WO 2011/085009, WO 2010/028189. On the one hand Grignard reagents are expensive and generally not easy to prepare. More importantly Grignard reactions are exothermic in nature and pose safety risks and demand a more complex process control.
The preparation of cyclopropyl-naphthalene by catalytic decomposition of the corresponding pyrazolones synthesized from hydrochlorides of Mannich bases is disclosed by Shabarov et al. in Zhurnal Obshchei Khimii (1963), 33(7), 2119-2123. The disadvantage of this process is that the product is obtained in a low yield and significant formation of undesirable side products generally arise.
The object of the present invention is to overcome the above disadvantages and to provide an improved process.